Catalytic Asymmetric Spiroannulation to Access Polycyclic Spiro Enones via Transient Axial-to-Point Chirality Induction and Transfer.

Chiral spirocycles exhibit tremendous potential in drug discovery and asymmetric synthesis, owing to their unique three-dimensional rigid framework and superior stability. However, stereoselective construction of polycyclic spiro compounds through a single catalytic transformation remains a significant and enduring challenge, owing to steric hindrance and electronic effects. Here we report a Pd/Sadphos-catalyzed dynamic kinetic asymmetric cascade dearomative Heck/Tsuji-Trost reaction of racemic phenolic biaryls with 1,3-dienes, enabled by transient axial-to-point chirality induction and transfer via a dynamic kinetic asymmetric transformation (DyKAT) manifold. Over 40 valuable polycyclic spiro enones bearing three contiguous tertiary/quaternary stereocenters are afforded in moderate to high yields, with excellent regio-, diastereo- and enantioselectivity (up to 99% ee). This work provides a modular synthetic strategy for complex chiral spirocycles and expands the scope of transient chirality transfer chemistry.